This is an application for a Mentored Clinical Scientist Development Award. The primary objective is to prepare the applicant for a position as a Pathologist/Investigator with an independent research program. The major focus of the training program involves bench research, to broaden the knowledge and technical expertise of the applicant in molecular and cellular immunology, and to provide an opportunity to establish a solid record of accomplishment supported by high quality publications. Coursework, participation in seminars and journal clubs, and other activities are proposed as part of the training plan. The research proposal is focused on an investigation of the role of HLA-DO in the antigen processing pathway of B cells. The central hypothesis is that DO regulates the antigen processing function of B cells, preventing aberrant T cell-B cell interactions that can result in autoantibody responses. Three specific aims are proposed to investigate the role of DO in B cell antigen processing in vitro, in T-dependent humoral immune responses in vivo, and in preventing the development of spontaneous humoral autoimmunity.